The market for neuroscience and women's health drugs has been moving towards the use of dual serotonin and norepinephrine reuptake inhibitors (SNRI) for first line treatment of various indications, as evidenced by the recent development of SNRI's such as Venlafaxine and Duloxetine. This contrasts with the traditional use of selective serotonin reuptake inhibitors (SSRI). Although the side-effect profile of SSRI's and SNRI's are less severe as compared to older, tricyclic antidepressants compounds, there are still some undesirable side effects related to the selectivity or other neuronal receptor binding (muscarinic, histamine and alpha-adrenergic, etc.) of these SSNI's and SNRI's. Binding to these receptors can lead to side effects such as, dry mouth, drowsiness, appetitite stimulation and some cardiovascular risks.
The higher norepinephrine (NE) activity of SNRI's has also been implicated in a number of side effects and therefore limits their application. For example, the currently available SNRI's have limited application for the treatment of irritable bowel syndrome (IBS) because of the constipation side effect associated with higher NE activity. Another potential side effect of SNRI's is that at higher dosages there is a modest increase in diastolic blood pressure and this side effect is associated with higher NE activity. Further, potential overdose situations have been associated with excess adrenergic stimulation, seizures, arrhythmias, bradycardia, hypertension, hypotension and death.
What are needed are alternative compositions for treating conditions associated with serotonin and norepinephrine imbalances, by allowing serotonin and or norepinephrine re-uptake inhibition for efficacy with lower post synaptic receptor binding for reduced side-effects [(H. Hall, et al., Acta pharmacol et. toxicol. 1984, 54, 379-384)].